This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This proposal constitutes the crystallographic component of a collaboration among several research groups at the University of Washington (PIs Ethan Merritt, Dustin Maly, Fred Buckner, Wesley van Voorhis, Erkang Fan, Christophe Verlinde, Wim Hol). Access to SSRL beamlines will allow us to determine crystal structures of key proteins and protein:ligand complexes from a set of important eukaryotic pathogens. The previous 4 years of study has laid the groundwork for subsequent biochemical studies and structure-based drug design targeting the corresponding diseases. These include major world scourges (malaria, sleeping sickness, Chagas? disease) and other infections with a disproportionate impact on Third World health. Crystallography will be combined with the output of chemical modeling and biochemical screening to conduct ligand discovery, to identify potential drug leads, and to provide SAR for the development of candidate drugs.